The long-term objective of this grant is to advance understanding of the etiologic role of obstetric complications (OCs), and their relation to brain and neuropsychological abnormalities in schizophrenia. If OCs are shown to be etiologically significant it could have important health implications, by adding significantly to the knowledge on which improved treatment, and ultimately primary prevention, of the disorder are based. The specific aims are to investigate relations among these variables, using a research and methods that involve obtaining OC data on the births and pregnancies of (a) 120 schizophrenic probands aged 20/45, (b) 120 psychiatrically normal control probands matched for age, gender, ethnicity, and handedness, and (c) 120 of the schizophrenic probands' similarly matched non-psychotic siblings. Diagnoses will use DSM-IV criteria, based on structured diagnostic-interviews (SCID), supplemented by chart review. OC scores will be obtained by applying published rating scales to obstetrical information from interviews with subjects' mothers, as well as from obstetrical records. OC, diagnostic, and neuropsychological test assessments will be made blindly with respect to each other and to MRI (magnetic resonance imaging) volumetric measures of key brain regions, including temporal and frontal cortex, hippocampus, amygdala, and thalamus. We will test hypotheses that OC scores are significantly worse, and the volumes of key brain regions significantly lower, in schizophrenics than 'm either normal controls or patients' own siblings. We will also test whether OC scores are associated with the volume of key brain regions or with performance on particular types of neuropsychological tests. Key predictions of a "two-factor" etiologic model, in which OCs often interact with familial risk factors to produce schizophrenia, will also be tested.